Debrisoquine 4-hydroxylase is the only enzyme capable of metabolizing and inactivating drugs of which debrisoquine is a typical member. Debrisoquine is an adrenergic neuron blocking agent used in a number of countries to control blood pressure in hypertensive patients. In population studies of individuals given this drug, two distinct phenotypes have been described: the extensive metabolizers (EM) excrete 10 to 200 times more of the urinary metabolite 4-hydroxydebrisoquine than poor metabolizers (PM). In family studies the PM phenotype has been shown to behave as an autosomal recessive trait with an incidence between 5% and 10% in the white population of Europe and North America. The PM phenotype extends to the deficient metabolism of more than 20 commonly prescribed drugs (Idle et al, 1979, Drug Metab. Rev. 9, 301-317; Price-Evans, D. A. in Ethnic Differences in Reactions to Drugs and Xenobiotics, eds. Kalow et al, 491-526 Alan R. Liss, N.Y., 1986), including .beta.-adrenergic receptor blocking agents, antiarrhythmics, antidepressants, the hallucinogen 4-methoxyamphetamine, and commonly used drugs such as the antitussive opioid dextromethorphan. Clinical studies have shown that PM individuals are at high risk with regard to the development of adverse side effects from these and many other drugs (Davies et al, 1981, Br. J. Clin. Pharmacol. 11, 88-91; Meyer et al, 1986, Xenobiotica. 16, 449-464). However, a genetic basis for this drug oxidation defect was heretofore not demonstrated.